Biomedical subjects

Elena Perez-Nadales

Publications and source records attributed to Elena Perez-Nadales.

3 recordsLinked to original sources

PubMed2004

The Ras/Raf/ERK signalling pathway drives Schwann cell dedifferentiation.

Schwann cells are a regenerative cell type. Following nerve injury, a differentiated myelinating Schwann cell can dedifferentiate and regain the potential to proliferate. These cells then redifferentiate during the repair process. This behaviour is important for successful axonal repair, but the signalling pathways mediating the switch between the two differentiation states remain unclear. Sustained activation of the Ras/Raf/ERK cascade in primary cells results in a cell cycle arrest and has been implicated in the differentiation of certain cell types, in many cases acting to promote differentiation. We therefore investigated its effects on the differentiation state of Schwann cells. Surprisingly, we found that Ras/Raf/ERK signalling drives the dedifferentiation of Schwann cells even in the presence of normal axonal signalling. Furthermore, nerve wounding in vivo results in sustained ERK signalling in associated Schwann cells. Elevated Ras signalling is thought to be important in the development of Schwann cell-derived tumours in neurofibromatosis type 1 patients. Our results suggest that the effects of Ras signalling on the differentiation state of Schwann cells may be important in the pathogenesis of these tumours.

Animals↗

PubMed2004

Essential function for ErbB3 in breast cancer proliferation.

The overexpression of the ErbB family of tyrosine kinase receptors is thought to be important in the development of many breast tumours. To date, most attention has focused on the ErbB2 receptor. Now, in a recent report, it has been shown that ErbB3 is a critical partner for the transforming activity of ErbB2 in breast cancer cells. Importantly, the proliferative signals from this transforming complex appear to act via the PI-3 kinase pathway.

Journal Article↗

PubMed2003

Dissecting the contribution of p16(INK4A) and the Rb family to the Ras transformed phenotype.

Although oncogenic Ras commonly contributes to the development of cancer, in normal primary cells it induces cell cycle arrest rather than transformation. Here we analyze the additional genetic changes required for Ras to promote cell cycle progression rather than arrest. We show that loss of p53 is sufficient for oncogenic Ras to stimulate proliferation in the absence of extrinsic mitogens in attached cells. However, surprisingly, we find that p53 loss is not sufficient for Ras to overcome anchorage dependence or contact inhibition. In contrast, expression of simian virus 40 (SV40) large T antigen (LT) allows Ras to overcome these additional cell cycle controls. Mutational analysis of SV40 LT shows that this action of SV40 LT depends on its ability to inactivate the retinoblastoma (Rb) family of proteins, in concert with the loss of p53. Importantly, we show that inactivation of the Rb family of proteins can be mimicked by loss of the cyclin-dependent kinase inhibitor p16(INK4A). p16(INK4A) is commonly lost in human tumors, but its contribution to the transformed phenotype is unknown. We demonstrate here a role for p16(INK4A) in the loss of cell cycle controls required for tumorigenesis and show how accumulating genetic changes cooperate and contribute to the transformed phenotype.

Animals↗